Non-alcoholic steatohepatitis (NASH) is a common disease and feeding mice a methionine-choline-deficient (MCD) diet is a frequently used model to study its pathophysiology. Genetic and environmental factors influence NASH development and liver lipid content, which was studied herein using C57BL/6 J mice bred in two different animal facilities. Age-matched male C57BL/6 J mice bred in two different animal facilities (later on referred to as WT1 and WT2) at the University Hospital of Regensburg were fed identical MCD or control chows for 2 weeks. Hepatic gene and protein expression and lipid composition were determined. NASH was associated with increased hepatic triglycerides, which were actually higher in WT1 than WT2 liver in both dietary groups. Cholesterol contributes to hepatic injury but was only elevated in WT2 NASH liver. Ceramides account for insulin resistance and cell death, and ceramide species d18:1/16:0 and d18:1/18:0 were higher in the NASH liver of both groups. Saturated sphingomyelins only declined in WT1 NASH liver. Lysophosphatidylcholine concentrations were quite normal in NASH and only one of the 12 altered phosphatidylcholine species declined in NASH liver of both groups. Very few phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol species were comparably regulated in NASH liver of both animal groups. Seven of these lipid species declined and two increased in NASH. Notably, hepatic mRNA expression of proinflammatory (F4/80, CD68, IL-6, TNF and chemerin) and profibrotic genes (TGF beta and alpha SMA) was comparable in WT1 and WT2 mice. Mice housed and bred in different animal facilities had comparable disease severity of NASH whereas liver lipids varied among the groups. Thus, there was no specific lipid signature for NASH in the MCD model.

中文翻译：

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饲喂蛋氨酸-胆碱缺乏饮食并饲养在不同动物设施中的年龄匹配的雄性小鼠肝脂质种类的变化

非酒精性脂肪性肝炎（NASH）是一种常见疾病，给小鼠喂食甲硫氨酸-胆碱缺乏症（MCD）饮食是研究其病理生理学的常用模型。遗传和环境因素影响NASH发育和肝脂质含量，本文使用在两种不同动物设施中饲养的C57BL / 6 J小鼠进行了研究。在雷根斯堡大学医院的两种不同的动物设施（后来称为WT1和WT2）中繁殖的年龄匹配的雄性C57BL / 6 J小鼠接受了相同的MCD或对照食物喂养2周。测定肝基因和蛋白质表达以及脂质组成。NASH与增加的肝甘油三酯有关，在两个饮食组中，WT1肝脏中的甘油三酸酯实际上都高于WT2肝脏。胆固醇有助于肝损伤，但仅在WT2 NASH肝脏中升高。神经酰胺导致胰岛素抵抗和细胞死亡，两组的NASH肝脏中神经酰胺种类d18：1/16：0和d18：1/18：0较高。饱和鞘磷脂仅在WT1 NASH肝脏中下降。在NASH中，溶血磷脂酰胆碱的浓度非常正常，两组NASH肝脏中只有12种改变的磷脂酰胆碱物种之一下降。在两个动物组的NASH肝脏中，很少有磷脂酰乙醇胺，磷脂酰丝氨酸和磷脂酰肌醇被调节。这些脂质种类中有7种在NASH中下降，而2种在上升。值得注意的是，在WT1和WT2小鼠中，促炎（F4 / 80，CD68，IL-6，TNF和凯莫瑞）和促纤维化基因（TGFβ和αSMA）的肝mRNA表达相当。在不同动物设施中饲养和繁殖的小鼠的NASH病情严重程度相当，而各组之间的肝脂质差异很大。因此，在MCD模型中没有针对NASH的特异性脂质签名。